The goal of project 1 was to explore the usefulness of a new class of macromolecules, starburst dendrimers, as renal function imaging agents. As a joint research project with Dr. Otto Gansow's group, two of dendrimer- chelate, DAB-PA16-CHX-A-DTPA-111 In (Ca2+, or In3+ saturated, DAB) and PAMAM-CHX-A-DTPA-111 In (Ca2+, PAMAM), were injected IV in normal male Sprague-Dawley rats. The plasma disappearance, biodistribution in the kidneys, liver and other organs were quantitated by direct tissue radioassay. The renal uptake and whole body clearance were carried out by camera-computer techniques. The renal uptake of the radioactive dendrimers was very fast with a half-time of only 6-9 min and the maximum uptake appeared at about 30 min postinjection. The activity in the kidneys at 2 hr was 26-31%ID/g tissue, much higher than that of 3-5%ID/g in the liver. However, when the whole organs were considered, the radioactivity in the kidneys was 42%ID/organ compared with 27%ID/organ for the liver. With PAMAM the liver activity was prohibitively high. The whole body retention in the rats with DAB remained unchanged up to 24 hr indicating no renal excretion. In view of these problems, these experiments were postponed until a more favorable dendrimer-chelate is synthesized In the second project, the pharmacokinetics and organ distribution of radioiodinated granulocyte colony-stimulating factor (G-CSF) were defined in rats. Despite the widespread clinical use of this factor in stimulating granulocyte proliferation in bone marrow transplantation, cytotoxic chemotherapy, AIDS and severe infections, little is known about its distribution in different organs. Thirty six rats were divided into two groups and IV injected with O.O3ug/kg (Group 1) or 5Oug/kg (Group2) of G- CSF. Serial whole blood and plasma samples were collected at various times for counting. The rats were sacrificed at various times and the concentration of 125I-G-CSF in different organs was quantitated by direct tissue radioassay. The disappearance of activity from the plasma best fitted a double exponential function. The half-life of the fast component was similar for the two groups but the half-life of the slow component was prolonged to 14 hr in Group 2, compared with 8 hr for Group 1. Despite the potent effect of this growth factor on granulopoiesis, its concentration in the marrow was relatively low, its highest uptake was in the liver. The principal route of excretion was the gastrointestinal tract. A full description of this work is now in preparation for publication.